Our initial studies suggest that the development of resistance to vinblastine in our in vitro cell lines may be related to membrane associated transport processes. We intend to further elucidate this by investigating the binding and/or transport properties of isolated membranes and membrane fractions, hopefully to the isolation of the specific site or sites involved. Related to this is the question of why vincristine is not a competitive inhibitor of vinblastine, and we will explore this further. Since the purported site of action of the Vincas is the protein tubulin (by blocking its normal polymerization processes) we will evaluate the binding properties of this protein derived from both cell lines, to see if it is involved in resistance development. The differences found between vinblastine uptake in our cell system, and vincristine uptake in the P-388/L1210 system raise the question of whether these are due to the drugs themselves, or more likely to differences in the cells. We will evaluate the uptake and binding to both membranes and tubulin of vinblastine in the P388/L1210 system, and make some direct comparisons, to delineate the exact source of the variance seen.